3-46372790-G-T

Variant names:

• chr3-46372790-G-T
• rs3176763
• NM_001394783.1:c.-11-102G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001394783.1(CCR5):​c.-11-102G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0186 in 784,414 control chromosomes in the GnomAD database, including 1,413 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.063 (998 hom., cov: 32)
  • Exomes 𝑓: 0.0079 (415 hom.)
• Consequence: CCR5 NM_001394783.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.768
• Publications: 10 publications found

Genes affected

CCR5 (HGNC:1606): (C-C motif chemokine receptor 5) This gene encodes a member of the beta chemokine receptor family, which is predicted to be a seven transmembrane protein similar to G protein-coupled receptors. This protein is expressed by T cells and macrophages, and is known to be an important co-receptor for macrophage-tropic virus, including HIV, to enter host cells. Defective alleles of this gene have been associated with the HIV infection resistance. The ligands of this receptor include monocyte chemoattractant protein 2 (MCP-2), macrophage inflammatory protein 1 alpha (MIP-1 alpha), macrophage inflammatory protein 1 beta (MIP-1 beta) and regulated on activation normal T expressed and secreted protein (RANTES). Expression of this gene was also detected in a promyeloblastic cell line, suggesting that this protein may play a role in granulocyte lineage proliferation and differentiation. This gene is located at the chemokine receptor gene cluster region. An allelic polymorphism in this gene results in both functional and non-functional alleles; the reference genome represents the functional allele. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2015]

CCR5AS (HGNC:54398): (CCR5 antisense RNA)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCR5	NM_001394783.1	c.-11-102G>T		intron_variant	Intron 1 of 1	ENST00000292303.5	NP_001381712.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCR5	ENST00000292303.5	c.-11-102G>T		intron_variant	Intron 1 of 1	1	NM_001394783.1	ENSP00000292303.4

Frequencies

GnomAD3 genomes AF: 0.0626 AC: 9519 AN: 152016 Hom.: 983 Cov.: 32

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0273

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00125

Gnomad OTH AF: 0.0473

GnomAD4 exome AF: 0.00790 AC: 4995 AN: 632280 Hom.: 415 Cov.: 8 AF XY: 0.00679 AC XY: 2224 AN XY: 327454

African (AFR) AF: 0.218 AC: 3629 AN: 16628

American (AMR) AF: 0.0161 AC: 406 AN: 25216

Ashkenazi Jewish (ASJ) AF: 0.000134 AC: 2 AN: 14958

East Asian (EAS) AF: 0.00 AC: 0 AN: 35172

South Asian (SAS) AF: 0.000491 AC: 23 AN: 46842

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37544

Middle Eastern (MID) AF: 0.0131 AC: 30 AN: 2290

European-Non Finnish (NFE) AF: 0.000828 AC: 349 AN: 421664

Other (OTH) AF: 0.0174 AC: 556 AN: 31966

GnomAD4 genome AF: 0.0629 AC: 9564 AN: 152134 Hom.: 998 Cov.: 32 AF XY: 0.0607 AC XY: 4513 AN XY: 74384

African (AFR) AF: 0.216 AC: 8949 AN: 41456

American (AMR) AF: 0.0272 AC: 416 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10586

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.00125 AC: 85 AN: 68012

Other (OTH) AF: 0.0468 AC: 99 AN: 2114

Alfa AF: 0.0371 Hom.: 90

Bravo AF: 0.0731

Asia WGS AF: 0.0160 AC: 55 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.23
DANN	Benign	0.39
PhyloP100		-0.77
PromoterAI		-0.0024	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3176763; hg19: chr3-46414281; COSMIC: COSV52751514;